1. Field of the Invention
The present invention relates to methods of diagnosing and prognosing Alzheimer's Disease.
2. Description of Prior Art
Alzheimer's Disease is a complex disease that affects the brain. Alzheimer's Disease is one of several disorders that cause the gradual loss of brain cells and is one of and possibly the leading cause of dementia. Dementia is an umbrella term for several symptoms related to a decline in thinking skills. Common symptoms include a gradual loss of memory, problems with reasoning or judgment, disorientation, difficulty in learning, loss of language skills and a decline in the ability to perform routine tasks. People with dementia also experience changes in their personalities and experience agitation, anxiety, delusions, and hallucinations.
It is important for a physician to determine the cause of memory loss or other symptoms. Some dementia or dementia-like symptoms can be reversed if they are caused by treatable conditions such as depression, drug interaction, thyroid problems and certain vitamin deficiencies.
Alzheimer's Disease advances at widely different rates. The duration of the illness may often vary from three to twenty years. The areas of the brain that control memory and thinking skills are affected first but as the disease progresses, cells also die in other regions of the brain. Eventually the person with Alzheimer's will need complete care. If the individual has no other serious illness, loss of brain function itself will cause death.
An early diagnosis of Alzheimer's Disease has many advantages including additional time to make choices that maximize quality of life, lessen anxieties about unknown problems, a better chance of benefiting from treatment and more time to plan for the future.
It is recognized that there is no one diagnostic test that can detect if a person has Alzheimer's Disease. The diagnostic process involves several kinds of tests and may take more than one day. Evaluations typically include consultation with a primary care physician and/or neurologist, a mental status evaluation to assess sense of time and place, ability to remember, understanding, communicate and the ability to do simple math problems, a series of evaluations that test memory reasoning, vision motor coordination of language skills, an examination that tests sensation, balance and other functions of the nervous system, a brain scan to detect other causes of dementia such as a stroke, laboratory tests such blood and urine tests to provide additional information about problems other than Alzheimer's that may be causing dementia and a psychiatric evaluation which provides an assessment of mood and other emotional factors that could cause dementia-like symptoms or may accompany Alzheimer's Disease.
There are a few proposed methods in the prior art for the diagnosis of Alzheimer's Disease. One such method is disclosed in U.S. Pat. No. 5,508,167 to Roses, et al. Roses, et al. discloses a method of diagnosing or prognosing Alzheimer's Disease involving directly or indirectly detecting the presence or absence of an apolipoprotein E-type 4 isoform or DNA encoding apolipoprotein E-type 4 in the subject. The presence of ApE4 indicates that the subject is at higher risk of getting afflicted with Alzheimer's Disease. The patent discloses an immunochemical assay for detecting the presence or absence of the apolipoprotein E4 allele in a subject.
Another method for a differential diagnosis of Alzheimer's dementia is disclosed in U.S. Pat. No. 6,451,547 to Jackowski, et al. The method involves directly detecting the presence of a biochemical marker, specifically human glutamine synthetase in bodily fluids such as blood or blood products. The detection is by an immuno assay incorporating antibody specific to human glutamine synthetase.
An additional method for diagnosing Alzheimer's Disease is disclosed in U.S. Pat. No. 6,495,335 to Chojkier, et al. The patent discloses modified beta-amyloid peptide antibodies that specifically bind the modified amyloid peptides, and methods for using the compositions in the diagnosis of Alzheimer's Disease.
An additional method for diagnosis of Alzheimer's Disease is disclosed in U.S. Pat. No. 5,492,812 to Vooheis. The patent discloses the diagnosis of Alzheimer's Disease based on proteolytic fragments the amino and carboxy terminal amino acid residues of tau proteins that are released from neurofibrillary tangles associated with disease which can be detected in bodily fluids outside the brain.
Although methods disclosed in the prior art are somewhat efficacious in diagnosing Alzheimer's Disease, there remains a need for improved methods and differentiation of Alzheimer's Disease. A major hurdle in developing anti-Alzheimer's Disease drugs has been the lack of means to identify the various subgroups of this heterogeneous disorder and of reliable molecular markers of neurodegeneration that can be monitored in living patients. Thus, to date, all anti-Alzheimer's Disease drugs were developed based on improvement in clinical symptoms i.e. activities of daily living and or cognition as determined by a battery of psychometric tests. Whether these first generation of anti-Alzheimer's Disease drugs, commonly referred to as symptomatic drugs, inhibit the disease process is not known. The present invention demonstrates that there are various distinct patterns of neurodegeneration in Alzheimer's Disease, i.e. subgroups of the disease which can be identified by monitoring the cerebrospinal fluid levels of Aβ1-42, tau and ubiquitin, and that the efficacy of therapeutic drugs can thus be monitored by the cerebrospinal fluid levels of these molecular markers.
3. Objects and Advantages
It is therefore a principal object and advantage of the present invention to provide a method for the diagnosis of Alzheimer's Disease.
It is another object of the present invention to provide a method for differentiating Alzheimer's Disease into subgroups.